irinotecan followed by fluorouracil in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i trial to study the effectiveness of irinotecan followed by fluorouracil in treating patients who have advanced solid tumors.

objectives: * determine the optimal dose of irinotecan when administered before fluorouracil in patients with advanced solid tumors. * determine the toxic effects of this regimen in these patients. * correlate the pharmacokinetics of irinotecan with its biologic effects in these patients. * assess, in a preliminary manner, the antitumor activity of this regimen in these patients. outline: this is a dose de-escalation study of irinotecan. patients receive irinotecan iv over 90 minutes on days 1, 8, 15, and 22 and fluorouracil iv over 5 minutes on days 2, 9, 16, and 23. treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. cohorts of 6 patients receive decreasing doses of irinotecan until the optimal dose is determined. the optimal dose is defined as the dose at which at least 3 of 6 patients show evidence of recruitment of cells into the s phase at 24 hours after irinotecan administration. projected accrual: a total of 18-24 patients will be accrued for this study within 12-18 months.

Eligibility criteria:
disease characteristics: * histologically proven recurrent or metastatic solid tumor that is not amenable to curative surgery, radiotherapy, or conventional chemotherapy of proven value * must have disease that can be safely and readily biopsied under local anesthesia (including, but not limited to, subcutaneous metastases, superficial lymph node metastases, or ascites) patient characteristics: age: * 18 and over performance status: * ecog 0-2 life expectancy: * at least 3 months hematopoietic: * wbc at least 4,000/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 times upper limit of normal (uln) * ast less than 2 times uln * alkaline phosphatase less than 2 times uln * lactic dehydrogenase less than 2 times uln renal: * creatinine no greater than 1.5 times uln other: * hiv negative * no active uncontrolled bacterial, viral, or fungal infection * no nonmalignant systemic disease that would preclude study participation * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * not specified chemotherapy: * see disease characteristics * at least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * no prior irinotecan endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy except small-port radiotherapy for local control * no concurrent radiotherapy except small-port radiotherapy for local disease control (e.g., pain relief or impending fracture) surgery: * see disease characteristics * at least 2 weeks since prior major surgery other: * no concurrent anticoagulants except warfarin or subcutaneous heparin

Keywords: unspecified adult solid tumor, protocol specific